A major challenge in biology is to understand how cells of the early mammalian embryo and their in vitro derivatives, namely embryonic stem (ES) cells, execute the diverse gene expression programs that lead to cellular specification. While the regulation of chromatin structure is necessary for the establishment and maintenance of heritable gene expression patterns during development, this process remains poorly understood. The overall goals of the lab are to determine how chromatin is organized during early development, to learn how these states are reprogrammed during differentiation, and to understand how failure to establish proper chromatin states can contribute to disease. We are particularly interested in investigating the mechanisms by which the non-allelic histone variants, such as the essential histone H2A variant H2AZ, may contribute to particular chromatin states. We will address these questions in ES cells using a combination of genomic, genetic, biochemical and cell biological tools to determine how histone variants influence chromatin structure, to determine how variants are recruited to discrete genomic sites, and to investigate how histone variants cooperate with other epigenetic regulators to control developmental gene expression patterns. These studies will provide new insights into the mechanisms by which chromatin states contribute to development and disease and for harnessing the potential of stem cells in medicine.